Pharmacy Perspectives - Summer/Fall 2017 - 6

Recent Research :

Compounds in Desert Creosote
Bush Could Treat Giardia and
"Brain-eating" Amoeba Infections



esearchers at Skaggs
School of Pharmacy
and Pharmaceutical
S c i en c e s at C U
and UC San Diego
(UCSD) have found
that compounds produced by the creosote bush, a desert plant
common to the southwestern United States,
exhibit potent anti-parasitic activity against
two deadly parasites. One of these parasites
(Giardia lamblia) is responsible for giardia
infections; the other, (Nagleria fowleri)
causes an often-lethal form of encephalitis.
Current treatment for both infections rely
on antibiotic and anti-parasitic drugs.
The findings, published online Aug. 9 in
PLOS Neglected Tropical Diseases, may give
researchers the chance to widen their arsenal
of antimicrobial agents, effective against deadly
parasitic infections.
The World Health Organization estimates
giardiasis, a diarrheal illness, is linked to approximately 846,000 deaths around the world
each year. Infection usually occurs through
ingestion of contaminated water or food.
Though rarely lethal in the United States, it's
estimated there are more than 1 million cases
of giardiasis in the country annually.
Infections due to N. fowleri, sometimes
called the 'brain eating amoeba,' are much
less common than Giardia. "However, it is a
far deadlier parasite. It is found in warm fresh
waters and infects the central nervous systems
of its victims through the nasal passages causing
lethal brain damage known as primary amoebic
meningoencephalitis (PAM)," said principal
investigator Dan LaBarbera, PhD, associate
professor of drug discovery and medicinal
chemistry, at CU Skaggs School of Pharmacy.
Due to N. flowleri's rapid infection cycle
and high mortality rate, the CDC has been
given special approval to provide the drug
miltefosine for clinicians to use as a treatment
option. But it is still not FDA approved and has
limited availability in the U.S. New compounds
derived from the creosote bush may provide less
expensive, and more effective treatment options.


LaBarbera and Anjan Debnath from
UCSD collaborated on this project as part
of the Skaggs Scholars program, funded by
The ALSAM Foundation. The program
matches investigators with complementary,
but different expertise, and is aimed at discovering breakthrough new drug therapies.
UCSD scientists provided expertise in
parasitology, while CU scientists provided
expertise in natural products and compound
libraries. The researchers developed an interest in these tropical diseases because of their
occurrence in Mexico and South America,
and because indigenous peoples have been
treating various infections with creosote
compounds for many years.
"The significance and intrigue of our
study is that it shows the value of prospecting for new medicines from plants
traditionally used by indigenous people as
medicine," said co-principal investigator
Anjan Debnath, PhD, an assistant adjunct
professor at UCSD.
The creosote bush is a tough evergreen
bush with a distinctive turpentine-like
scent. Native Americans in both the U.S.
and Mexico have long used the plant for
a variety of ailments, including intestinal
complaints. There is also an existing body
of scientific work documenting the plant's
pharmacologically active compounds, notably nordihydroguaiaretic acid (NDGA).
NDGA has antiviral, antibacterial, anti-inflammatory and anticancer properties.  The
study is the first to show that NDGA and
five other compounds also are active against
the two pathogenic parasites.
"In our study, NDGA proved to be a
more potent anti-parasitic agent against
N. fowleri compared to miltefosine,"
LaBarbera said. "Therefore, NDGA may
lead to a more effective drug therapy option
for N. fowleri infection."
 This research was funded, in part, by a grant
from The ALSAM Foundation and National
Institutes of Health (KL2TR001444).
Full study:

CU Skaggs School of Pharmacy and Pharmaceutical Sciences



aculty member Jacci
Bainbridge, PharmD, together
with Clinical Neurology
Research Fellow Matt Makelky,
PharmD, are currently studying
cannabis and its effectiveness
in treating a variety of conditions including
back pain, Parkinson's tremor and seizure disorders in children.
As some of the first prospective cannabis
trials on the Anschutz Medical Campus, these
studies "will hopefully help determine the
cannabis' effectives in treating these types of
disorders, side effects and dosing levels," says
Jacci Bainbridge.
Under the guidance of Emily Lindley, PhD
with the Department of Orthopedics, the
first of three studies compares cannabis to
oxycodone in patients with back pain. In this
study, patients and a control group without
the disease are given either oxycodone or cannabis with a dose of placebo drug, or a double
placebo dose. "Various cognitive tests will be
administered to see the degree of impairment,
and also there will be a test to see the degree
of pain reduction. Will the patients be able
to tell which drug they are being given? Will
cannabis give better pain relief? Which drug
affects cognition more? All interesting questions that we hope to answer with this study,"
says Bainbridge.
The second study, also sponsored by the
Colorado Department of Public Health and
Environment (CDPHE), is in phase III clinical
trials studying Epidiolex (CBD) in Parkinson's
Disease tremor and how CBD oral oil may help
control tremor symptoms. "We are especially
involved in the accuracy of the dosing of this
product and are looking at safety and efficacy,"
says Bainbridge who is working with Principal
Investigator Maureen Lehey, MD, at the
Movement Disorders clinic at the UCH outpatient pavilion.
Lastly, there is a trial at Children's Hospital for
CBD as add-on therapy in patients with tuberous
Sclerosis complex who experience inadequately-controlled seizures.  The product used for this
trial is Epidiolex (CBD), and is in phase III clinical
trials. Bainbridge and Makelky will act as the
dispensing pharmacists for this trial.

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